The goal of this research is to transform clinical care for patients with degenerative and traumatic bone pathologies. Despite recent advances in bone graft technology, a major void remains for orthopaedic surgeons who perform procedures that require bone healing. Current biologics on the market, such as recombinant human bone morphogenetic protein-2 (rhBMP-2; INFUSE(tm)), are effective but are associated with adverse effects. Ceramics and demineralized bone matrices (DBM) are insufficiently effective as bone graft substitutes for spine fusion. Our goal is to develop an exogenous growth factor-free ceramic composite scaffold that is safe, easy to manipulate, and more effective at inducing bone formation and spine fusion than currently available products. To this end, our group has developed a unique 3D-printable hydroxyapatite (HA) ink that can be used to create a robust composite scaffold that not only promotes bone regeneration, but also has hyperelastic mechanical properties that improves functionality and delivery in both open and minimally invasive spine fusion procedures. This 3D-printed technology is easily scalable and facilitates incorporation of other bioactive factors or drugs, since ink synthesis, 3D-printing, and processing are carried out at ambient temperatures. In preliminary work, we developed a strategy to 3D-print a variation on this hyperelastic HA (hHA) that incorporates demineralized bone matrix (DBM) particles into the 3D-ink, which imparts an added osteoinductive stimulus from the native bioactive growth factors present within the DBM. The result is a flexible and elastic hHA-DBM composite that we believe is the basis for a highly effective bone graft substitute for both open and minimally invasive spine fusion procedures. With this proposal, we will 1) develop the optimal 3D-ink formulation and printing parameters for bone regeneration and evaluate the capacity of this hyperelastic bone composite (HBC) to elicit spine fusion in a rat spine fusion model; 2) compare its efficacy (bone regenerative and spine fusion capacities) with an established positive control (rhBMP-2; INFUSE(tm)); and 3) compare the mechanisms of pro-osteogenic action and inflammatory host response of the hyperelastic bone composite with that of rhBMP-2. We hypothesize that the resulting HBC will elicit comparable fusion rates and regenerative capacity to rhBMP-2, but will provoke a significantly lower inflammatory host response. This translational study aims to develop a technology that could modernize clinical care approaches, while advancing our understanding of the behavior and functionality of complex 3D-printed particle-based composites. Not only would this investigation lay the groundwork for a safe, efficacious, and cost-effective therapy for spinal arthrodesis, but the versatility of design and rapid rate of manufacturing would also allow for efficient customizabilit to individual patients. We expect that full development of this technology would transform clinical practice for patients with degenerative and traumatic conditions of the spine, and would ultimately translate to other orthopaedic and non-orthopaedic settings where bone regeneration is required.